Nitric oxide (NO) is a small biological arbitrator and signaling molecule that has numerous significant biological roles in our body. Most of the neurons produce NO by neuronal nitric oxide synthase (nNOS). NO has been involved in the regulation of neurogenesis, synaptic plasticity, learning, and memory. Also, it contributes to the regulation of circulation and synapses, cerebral map formation, and neuropeptides. In the current review, we focused on previous research that has demonstrated structural aspects, subcellular localization, and some factors that adjust nNOS function. Furthermore, we have characterized the effect of nNOS in the brain in some physiological situations, particularly long-term potentiation and depression (LTP and LTD) and neural plasticity during development. Moreover, the effect of NO on neuropeptidergic neurons, including orexin, in reward systems was reviewed. Also, this study has focused on the NO involvement in brain circulation, the excitability of neurons, and the homeostatic balance of excitatory and inhibitory signaling in the brain.